Therapeutic treatments on various diseases of mammals including man by inhibiting certain enzyme systems have hitherto been practiced widely. Thus, in therapeutically treating hypertension, cardiac failure and the like, medical treatments by administration of an enzyme inhibitor capable of inhibiting angiotensin-converting enzymes are well known. Most of such enzyme inhibitors have been derived through purely chemical synthetic routes. While, we have continued our investigations with the intention of looking for any useful enzyme inhibitor from among metabolic products of microorganisms. In the course of our investigations, we have already found that actinonin, the compound known as an antibiotic (see U.S. Pat. No. 3,240,787), inhibits a wide variety of peptidases (see "Journal of Antibiotics", 38, 1629-1630 (1985), Japanese Patent Application First Publication "Kokai" No. 15840/86 or U.S. Pat. No. 4,663,342 and JP-A "Kokai" No. 4228/86).
The previous syntheses of actinonin-related compounds have been carried out by purely synthetic means for the purpose of improving antibacterial activities of actinonin (see "Journal of the Chemical Society, Perkin Transactions 1", 1975, page 846).
We have further been proceeding with our investigations for the purpose of looking for useful enzyme inhibitors by chemical modification of actinonin with taking into consideration such fact that actinonin is obtainable by cultivating a strain of the genus Actinomycetes, Streptomyces roseopulratus at reasonable cost and that the molecule of actinonin has a peculiar structure consisting of L-prolinol which is obtained by the reduction of a natural amino acid, L-proline, and of a fatty acid hydroxamide. As a result, we have already found a class of actinonin derivatives which can strongly inhibit prolylendopeptidase (post-prolin-cleaving enzyme, see Japanese Patent Application First Publication "Kokai" No. 310864/88 or U.S. Pat. No. 4,929,633).
During our previous investigations on the production of novel enzyme inhibitors from which we seek for medicines useful for therapeutic treatments on such important diseases as hypertension, cardiac failure, etc., we have percieved that actinonin and derivatives thereof already known have such low levels of inhibitory activity against angiotensin-converting enzymes that are too low to be utilized in practice. Then, we have further continued our investigations on the syntheses of new actinonin derivatives with the view to providing new, useful actinonin derivatives having inhibitory activities against not only angiotensin-converting enzymes but also against enkephalinase. As a result, we have now succeeded in synthesizing a new class of actinonin derivatives having general formula (I) shown below and found them to have desired enzyme-inhibitory activities.